The overall objective of this program is to elucidate the metabolic patterns of protein and RNA synthesis and their control in eucaryotic cells. Specific attention is focused on the role of the ribosome in these processes. The basic research is through the study of conditional lethal mutants that are defective in RNA or protein synthesis. Antibiotics that affect RNA and protein synthesis are being used to study the control mechanisms that regulate these processes. Goals for current year: 1. Continue to screen our basic collection of conditional lethal mutants in yeast (1400 heat sensitive mutants and 100 cold sensitive mutants) for mutants blocked in RNA or protein synthesis. 2. Isolate a series of conditional lethal mutants from mammalian cell lines. 3. Develop a series of biochemical and physiological, in vivo, tests that will efficiently identify the precise site of action of antibiotics and antitumor agents. 4. Study the control mechanisms for rRNA and mRNA biosynthesis in mammalian cells and in yeast. We have taken advantage of our mutants defective in RNA biosynthesis in yeast in designing these studies.